Enzalutamide Antitumour Activity Against Metastatic Castration-resistant Prostate Cancer Previously Treated with Docetaxel and Abiraterone: A Multicentre Analysis.

Abstract

BACKGROUND:

The degree of antitumour activity of enzalutamide following disease progression on docetaxel and abiraterone remains controversial.

OBJECTIVE:

To examine the effect of enzalutamide in patients progressing following taxane-based chemotherapy and abiraterone.

DESIGN, SETTING, AND PARTICIPANTS:

Metastatic castration-resistant prostate cancer patients entering one of four European compassionate use programmes of enzalutamide.

OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS:

The primary end point was overall survival (OS). Secondary end points were association between OS and posttreatment prostate-specific antigen (PSA) kinetics, patient characteristics, and progression-free survival, respectively. Kaplan-Meier survival analysis and Cox proportional hazard analysis were performed.

RESULTS AND LIMITATIONS:

We identified 137 patients who prior to enzalutamide had progressed following a median of eight cycles of docetaxel and seven courses of abiraterone. The median time on enzalutamide was 3.2 mo; median OS from the time patients started enzalutamide was 8.3 mo (95% confidence interval, 6.8-9.8). Only 45 (38%) and 22 (18%) patients had PSA declines (unconfirmed) >30% and 50%, respectively. Patients who had more than 30% or 50% falls in PSA had improved survival compared with patients who had no such PSA fall (11.4 mo vs 7.1 mo; p=0.001 and 12.6 vs 7.4 mo; p=0.007, respectively). Poor performance status and low haemoglobin was negatively associated with OS.

CONCLUSIONS:

Median OS on enzalutamide following disease progression on taxane-based chemotherapy and abiraterone was modest, but patients who experience a PSA decline >30% or 50%, respectively, with enzalutamide in this setting had longer survival.

PATIENT SUMMARY:

Enzalutamide produces modest prostate-specific antigen (PSA) responses in patients progressing following chemotherapy and abiraterone. Despite a modest PSA response, survival may still be improved.

• Authors: Klaus Brasso, Frederik B Thomsen, Andres J Schrader, Sebastian C Schmid, David Lorente, Margitta Retz, Axel S Merseburger, Christoph A von Klot, Martin Boegemann, Johann de Bono
• Journal: European urology (Eur Urol) Vol. 68 Issue 2 Pg. 317-24 (Aug 2015) ISSN: 1873-7560 [Electronic] Switzerland
• PMID: 25108579 (Publication Type: Journal Article, Multicenter Study)
• Copyright: Copyright © 2014 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Chemical References

• Androgen Antagonists
• Androstenes
• Benzamides
• Nitriles
• Taxoids
• Docetaxel
• Phenylthiohydantoin
• enzalutamide
• KLK3 protein, human
• Kallikreins
• Prostate-Specific Antigen
• abiraterone

Topics

• Aged
• Aged, 80 and over
• Androgen Antagonists (adverse effects, therapeutic use)
• Androstenes (adverse effects, therapeutic use)
• Antineoplastic Combined Chemotherapy Protocols (adverse effects, therapeutic use)
• Benzamides
• Compassionate Use Trials
• Disease Progression
• Disease-Free Survival
• Docetaxel
• Drug Resistance, Neoplasm
• Drug Substitution
• Europe
• Humans
• Kallikreins (blood)
• Kaplan-Meier Estimate
• Male
• Middle Aged
• Nitriles
• Phenylthiohydantoin (adverse effects, analogs & derivatives, therapeutic use)
• Proportional Hazards Models
• Prostate-Specific Antigen (blood)
• Prostatic Neoplasms, Castration-Resistant (blood, drug therapy, mortality, pathology)
• Risk Factors
• Taxoids (adverse effects, therapeutic use)
• Time Factors
• Treatment Outcome